id: Q9NX36 gene_symbol: DNAJC28 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: DNAJC28 (C21orf55/C21orf78) is a poorly characterized member of the DnaJ/HSP40 (J-domain) co-chaperone family encoded on chromosome 21. It contains a canonical J domain together with a predicted coiled-coil region, and its N-terminus resembles a mitochondrial-targeting presequence, suggesting it may act as a mitochondrial J-domain co-chaperone. By analogy to other J-domain proteins it is presumed to assist HSP70-type chaperones in protein folding, but no substrate, partner chaperone, or cellular process has been experimentally established. It is expressed in brain, testis, uterus, spleen and liver (tissue-enhanced in testis) and is phosphorylated at Thr-347. existing_annotations: - term: id: GO:0001659 label: temperature homeostasis evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Phylogenetic (IBA) transfer of "temperature homeostasis" from a broad PANTHER family node. There is no experimental evidence that DNAJC28 participates in temperature homeostasis, and this protein is otherwise essentially uncharacterized. action: MARK_AS_OVER_ANNOTATED reason: The biological process is inferred only by phylogenetic grouping with distantly related family members; no direct or organism-specific evidence supports a role for DNAJC28 in temperature homeostasis. supported_by: - reference_id: file:human/DNAJC28/DNAJC28-uniprot.txt supporting_text: May have a role in protein folding or as a chaperone. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24407287 qualifier: enables review: summary: A single AgBase-curated interaction (with PYCARD/ASC, Q9ULZ3) reported in a study focused on PML and the ASC inflammasome. The bare protein binding term is uninformative and the interaction does not establish a chaperone function for DNAJC28. action: KEEP_AS_NON_CORE reason: Records a real but isolated interaction; bare protein binding is uninformative per curation guidelines and there is no specific molecular function that this single high-throughput hit justifies. supported_by: - reference_id: file:human/DNAJC28/DNAJC28-goa.tsv supporting_text: UniProtKB:Q9ULZ3 references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: PMID:24407287 title: Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation. reference_review: relevance: LOW correctness: VERIFIED review_notes: "Cached publication title matches the YAML title; this is a PML/ASC inflammasome study, NOT a DNAJC28-focused paper. It is the source of only a single GOA IPI 'protein binding' annotation (DNAJC28 with UniProtKB:Q9ULZ3), so it is correctly cited for that interaction but does not establish DNAJC28's molecular function or biological process. Sole literature reference for this poorly characterized gene; background relevance only." findings: [] - id: file:human/DNAJC28/DNAJC28-uniprot.txt title: UniProt entry Q9NX36 (DJC28_HUMAN), DnaJ homolog subfamily C member 28 findings: - statement: J-domain (HSP40) protein with a predicted coiled-coil; function annotated only as a possible role in protein folding or as a chaperone; expressed in brain, testis, uterus, spleen and liver; phosphorylated at Thr-347. reference_section_type: OTHER - id: file:human/DNAJC28/DNAJC28-hypotheses/jdomain-hpd-motif/openscientist.md title: 'OpenScientist hypothesis run: DNAJC28 J-domain HPD-motif check' findings: - statement: Structurally supports a functional J-domain co-chaperone - DNAJC28 has an intact HPD tripeptide (H79-P80-D81) in a canonically folded J-domain, sub-2 A RMSD to DNAJA1's Hsp70-interaction surface, and the HPD is conserved in 18/20 vertebrate orthologs; it is not a degenerate pseudo-co-chaperone. Caveat - no direct Hsp70 ATPase-stimulation assay has been published. supporting_text: DNAJC28 is a structurally competent Hsp70 co-chaperone, not a degenerate J-domain protein. core_functions: - description: J-domain (HSP40) co-chaperone. The J domain is structurally confirmed competent (intact HPD motif and canonical fold; sub-2 Angstrom RMSD to the Hsp70 interaction surface of DNAJA1), so it is predicted to engage HSP70-type chaperones to assist protein folding, though no substrate, partner, or direct ATPase- stimulation assay has yet been experimentally validated. Its N-terminal sequence suggests a mitochondrial localization. molecular_function: id: GO:0051087 label: protein-folding chaperone binding supported_by: - reference_id: file:human/DNAJC28/DNAJC28-uniprot.txt supporting_text: May have a role in protein folding or as a chaperone. - reference_id: file:human/DNAJC28/DNAJC28-hypotheses/jdomain-hpd-motif/openscientist.md supporting_text: All structural requirements for Hsp70 ATPase stimulation are met. proposed_new_terms: [] suggested_questions: - question: Is DNAJC28 a genuine mitochondrial J-domain co-chaperone, and which HSP70-type partner (e.g. mortalin/HSPA9) does it stimulate? - question: Does DNAJC28 have any client proteins or a defined cellular process, or is it functionally redundant/vestigial? suggested_experiments: - description: Subcellular fractionation and fluorescence microscopy of tagged DNAJC28 to test the predicted mitochondrial localization and import dependence on the N-terminal presequence. - description: In vitro HSP70 ATPase-stimulation assay with recombinant DNAJC28 (and HPD-motif mutant) to test whether the J domain is a functional co-chaperone. - description: Affinity purification-mass spectrometry of DNAJC28 to identify its chaperone partners and candidate clients beyond the single reported ASC interaction.